The proposed research will examine the usefulness of magnetoencephalography (MEG) as a technique for visualizing neuronal activity in the form of current patterns in the brain. Electric current is an important modality for imaging functions of the brain, since it reflects neuronal activity with a millisecond time resolution. However, there are still very few validation studies of MEG as a current source imaging technique using an animal model that is directly comparable to the human brain. We, therefore, propose to rigorously evaluate the accuracy of MEG in identification of electrically active neuronal tissues in a gyrencephalic brain. MEG will be evaluated in comparison with electroencephalography (EEG), since MEG and EEG are closely related complementary techniques for inferring current source distributions. The MEG and EEG will be evaluated by studying the somatic evoked fields (SEFs) and potentials (SEPs) of an in vivo swine preparation that has a large, well-developed gyrencephalic brain. the somatosensory cortex receiving projections from the snout will be activated by electrical stimulations of the afferents. The resulting SEF will be measured over the exposed intact scalp (with hairs removed), intact skull and intact dura at a measurement distance of 2 mm from each of these surfaces, using a high-resolution, 4-channel superconducting MEG sensor. The SEP will be also measured from the same animal over the scalp, exposed skull, and exposed cortex at nearly 100 locations, using a multi-channel array of electrodes. The active sites will be deduced during the experiment and intracortical electrodes will be inserted at inferred active locations in the cortex to determine whether there are polarity reversals in the laminar field potential profile. Preliminary experiments indicate that these measurements are feasible within the same preparation. The accuracy of localization will be evaluated not only with electrocorticogram (ECoG) and the intracortical recordings, but also with pharmacological and surgical lesions of the active sites or surrounding presumably non-active regions. In some experiments extracellular unit recordings will be carried out. After these measurements, the brain will be photographed and the shape of the dorsal surface of the brain will be determined with a laser-beam scanner for the purpose of calibrating the histological 3-D reconstruction of the brain and, in some cases, for calibrating the 3-D reconstruction of the MRI image of the brain. At the end of the experiment the animal will be euthanized and the perfused brain will be removed for a 3-D histological reconstruction to correlate with the locations of active sites deduced from the MEG and EEG measurements. Such comparisons will be carried out on the normal brain and on brains with lesions in the cortex to infer the effect of mass lesions on the accuracy of source localization in human MEG studies. Various algorithms will be evaluated for their accuracy in identifying locations of single and multiple active sites, since our preparation is ideal for direct evaluations. The algorithms to be tested will include not only the conventional single and multiple dipole models, but also the multiple signal classification (MUSIC) method and covariance methods employing Wiener filter.